Methicillin-resistant Staphylococcus Aureus Bloodstream Infections Research Articles

Healthcare-associated infections and antimicrobial resistance in Canadian acute care hospitals, 2017-2021.

Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) continue to contribute to excess morbidity and mortality among Canadians. This report describes epidemiologic and laboratory characteristics and trends of HAIs and AMR from 2017 to 2021 (Candida auris 2012-2021) using surveillance and laboratory data submitted by hospitals to the Canadian Nosocomial Infection Surveillance Program (CNISP) and by provincial laboratories to the National Microbiology Laboratory (NML). Data collected from 88 Canadian sentinel acute care hospitals between January 1, 2017, and December 31, 2021, for Clostridioides difficile infections (CDI), carbapenemase-producing Enterobacterales (CPE), methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) and vancomycin-resistant Enterococcus (VRE) BSIs. Candida auris (C. auris) surveillance was initiated in 2019 by CNISP and in 2012 by the NML. Case counts, rates, outcomes, molecular characterization and antimicrobial resistance profiles are presented. From 2017 to 2021, increased rates per 10,000 patient days were observed for MRSA BSIs (35%; 0.84-1.13), VRE BSIs (43%; 0.23-0.33) and CPE infections (166%, 0.03-0.08). CDI rates decreased 11% (5.68-5.05). Thirty-one C. auris isolates were identified in Canada from 2012 to 2021, with the majority from Western Canada (68%). From 2017 to 2021, the incidence of MRSA and VRE BSIs, and CPE infections increased in Canadian acute care hospitals participating in a national sentinel network (CNISP) while CDI decreased. Few C. auris isolates were identified from 2012 to 2021. Reporting standardized surveillance data and the consistent application of infection prevention and control practises in acute care hospitals are critical to help decrease the burden of HAIs and AMR in Canada.

Epidemiology and risk factors for mortality among methicillin-resistant Staphylococcus aureus bacteremic patients in Southern Brazil.

This study aimed to evaluate the epidemiology and 30-day mortality of adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We retrospectively reviewed the demographic and clinical data of adult patients with S. aureus bloodstream infections (BSI), admitted to a tertiary public teaching medical center in Porto Alegre, Southern Brazil, from January 2014 to December 2019. A total of 928 patients with S. aureus BSI were identified in the study period (68.5 per 100,000 patient-years), and the proportion of MRSA isolates was 22% (19-27%). Thus, 199 patients were included in the analyses. The median age was 62 (IQR: 51-74) years, Charlson Comorbidity Index (CCI) median was 5 (IQR: 3-6), the Pitt bacteremia score (PBS) median was 1 (IQR: 1-4), and the most common site of infection was skin and soft tissue (26%). Most infections were hospital-acquired (54%), empirical anti-MRSA treatment was initiated in 34% of the cases, and in 44% vancomycin minimum inhibitory concentration was 1.5mg/L or above. Sixty-two (31.2%) patients died up to 30 days after the bacteremia episode. Patients with more comorbid conditions (higher CCI; aOR 1.222, p = 0.006) and a more severe presentation (higher PBS; aOR 1.726, p<0.001) were independently associated with mortality. Empiric antimicrobial therapy with an anti-MRSA regimen was associated with reduced mortality (aOR 0.319, p = 0.016). Our study identified significant risk factors for 30-day mortality in patients with MRSA BSI in a population with a high incidence of S. aureus bacteremia. Empiric treatment with an anti-MRSA drug was a protective factor. No significant variation in the incidence of S. aureus BSI was recorded throughout the period.

A retrospective analysis of clinical characteristics and prognostic factors for 152 cases of Staphylococcus aureus bloodstream infection

To understand the clinical characteristics of Staphylococcus aureus bloodstream infection and the main risk factors affecting clinical prognosis, providing a reference for clinical prevention and control of Staphylococcus aureus bloodstream infection. In this study, the clinical data of 152 patients with Staphylococcus aureus bloodstream infection admitted to Guangdong Provincial People's Hospital from January 2019 to December 2021 were retrospectively analyzed by reviewing the electronic medical record system, including underlying diseases, clinical characteristics, risk factors, and bacterial resistance. Statistical methods such as Chi-Squared Test and t Test were used to analyze the related risk factors that may affect the clinical characteristics and prognosis of patients with Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection, then the variables with P<0.05 in univariate analysis were included in the multivariate logistic regression model to analyze the independent risk factors of poor prognosis. The results showed among 152 patients with Staphylococcus aureus bloodstream infection, 50 patients (32.89%) were infected with MRSA. In comparison, 102 patients (67.11%) were infected with methicillin-sensitive Staphylococcus aureus (MSSA). Except for rifampicin, the resistance rate of MRSA to commonly used antibiotics was all higher than that of MSSA, and the difference was statistically significant (Chi-square values were 8.272, 11.972, 4.998, 4.776, respectively;all P-values are less than 0.05). Strains resistant to vancomycin, linezolid, and quinupristin/dalfopristin were not found. In the MRSA group, indwelling catheter and drainage tube, carbapenems, and β-lactamase inhibitor treatment were significantly higher than the MSSA group. The difference was statistically significant (P<0.05). The incidence of poor prognosis of bloodstream infection in the MRSA group was higher than that in the MSSA group (34.00% vs 13.73%), and the difference was statistically significant (χ2=8.495, P<0.05). No independent risk factors associated with poor prognosis were found in the included patients with MRSA bloodstream infection.Multivariate Logistic regression model analysis showed that solid malignant tumors (OR=13.576, 95%CI: 3.352-54.977, P<0.05), mechanical ventilation (OR=7.468, 95%CI: 1.398-39.884, P<0.05) were the most important independent risk factors for poor prognosis in patients with Staphylococcus aureus bloodstream infection. In summary, the poor prognosis rate of MRSA bloodstream infection is higher than that of MSSA. The clinical evaluation of related risk factors should be strengthened, targeted prevention and control interventions should be taken to improve the prognosis of patients with Staphylococcus aureus bloodstream infection, and the use of antibiotics should be rational and standardized, to control bacterial infection and drug resistance effectively.

Derivation and Validation of a Risk Score for Methicillin-Resistant Staphylococcus aureus Bloodstream Infection.

Compared with methicillin sensitive Staphylococcus aureus (MSSA), the prognosis of patients with methicillin resistant Staphylococcus aureus (MRSA) bloodstream infection is poor. Therefore, the construction of MRSA and MSSA identification model has certain value for the selection of antibiotics and treatment outcome control. This study aimed to derive and validate a simple risk prediction model for MRSA bloodstream infection in Chinese patients. Three hundred and thirty-five patients with Staphylococcus aureus (S. aureus) bloodstream infection were retrospectively analyzed and divided into three groups. The first group was used for the risk score derivation (n = 163), the second group was used for internal validation (n = 80), and the third group was used for external validation (n = 92). According to the odds ratio (OR) obtained from multivariate logistic regression, the risk prediction model for MRSA bloodstream infection was established, and the prediction efficiency of the model in three cohorts were evaluated. Hospital stay before BSI ≥ 7 days, hospital acquired BSI, infection source ≥ 2 sites, indwelling gastric tube before BSI and carbapenems used before BSI and after admission were independent influencing factors of MRSA in the derivation group, the above influencing factors were scored 3, 5, 4, 3, and 3, respectively. The derivation, internal and external validation groups showed adequate discrimination (the AUCs were 0.788, 0.780, and 0.742, respectively) and good calibration (H-L tests were χ2 = 3.896, p = 0.306; χ2 = 4.221, p = 0.298; and χ2 = 3.974, p = 0.352, respectively). The risk scores were further divided into very low-risk (score 0 - 3), low-risk (score 4 - 7), high-risk (score 8 - 12), and very high-risk (score ≥ 13) layers. The simple risk score model for predicting MRSA bloodstream infection has good predictive effect, high predictive accuracy, and good clinical applicability, which can help clinicians choose sensitive antibiotics and reduce the adverse prognosis of patients.

204. Genomic comparison of blood and colonizing nasal isolates in patients hospitalized with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of health-care associated infections, particularly bloodstream infections (BSI). Concomitant colonization of the anterior nares has been shown to have implications on persistence, recurrence, and transmission events. We performed genomic comparisons between paired nasal and blood MRSA isolates obtained from the same patient to elucidate the genetic differences that may contribute to within-host invasion and virulence. Methods Patients hospitalized with MRSA bloodstream infection were swabbed in the bilateral nares. Paired blood and nasal isolates underwent DNA extraction and spa typing. Nasal and blood isolates from the same patients with matching spa types were sequenced by Illumina and PacBio respectively. For genomic analysis, PathoSPOT and Snippy were used to compare genomes of nasal and blood isolate pairs to evaluate single nucleotide polymorphisms, insertions and deletions. Results Of 121 patients with MRSA BSI, 87 patients (72%) had concomitant colonization of the anterior nares with MRSA. Spa type of t002 predominated in both blood and nasal isolates. From the 76 pairs that underwent genomic analysis, several mutated genes were identified across all pairwise comparisons, 8 of which recurred in more than one patient pair. These included genes involved in conferring antibiotic resistance, increased mutability, immune evasion, and adaptive metabolism. Conclusion In patients with MRSA BSI and concomitant MRSA nasal colonization, mutations identified by genomic analysis in blood-nasal pairs are implicated in contributing to invasion and within-host adaptability. Disclosures All Authors: No reported disclosures.

Molecular Epidemiology, Antimicrobial Susceptibility, and Clinical Features of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections over 30 Years in Barcelona, Spain (1990-2019).

Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSI) are a significant cause of mortality. We analysed the evolution of the molecular and clinical epidemiology of MRSA-BSI (n = 784) in adult patients (Barcelona, 1990−2019). Isolates were tested for antimicrobial susceptibility and genotyped (PFGE), and a selection was sequenced (WGS) to characterise the pangenome and mechanisms underlying antimicrobial resistance. Increases in patient age (60 to 71 years), comorbidities (Charlson’s index > 2, 10% to 94%), community-onset healthcare-associated acquisition (9% to 60%), and 30-day mortality (28% to 36%) were observed during the 1990−1995 and 2014−2019 periods. The proportion of catheter-related BSIs fell from 57% to 20%. Current MRSA-BSIs are caused by CC5-IV and an upward trend of CC8-IV and CC22-IV clones. CC5 and CC8 had the lowest core genome proportions. Antimicrobial resistance rates fell, and only ciprofloxacin, tobramycin, and erythromycin remained high (>50%) due to GyrA/GrlA changes, the presence of aminoglycoside-modifying enzymes (AAC(6′)-Ie-APH(2″)-Ia and ANT(4′)-Ia), and mph(C)/msr(A) or erm (C) genes. Two CC22-IV strains showed daptomycin resistance (MprF substitutions). MRSA-BSI has become healthcare-associated, affecting elderly patients with comorbidities and causing high mortality rates. Clonal replacement with CC5-IV and CC8-IV clones resulted in lower antimicrobial resistance rates. The increased frequency of the successful CC22-IV, associated with daptomycin resistance, should be monitored.

Clinical characteristics of and risk factors for secondary bloodstream infection after pneumonia among patients infected with methicillin-resistant Staphylococcus aureus

PurposeTo investigate the clinical features and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia (MP) with secondary MRSA bloodstream infections (MRSA-BSI) (termed MP-BSI) compared with MP alone and to study the incidence of MP-BSI among patients with MP. MethodsThis was a retrospective, single-center study with clinical data derived from previous medical records. The cases were divided into groups: MP alone and MP-BSI. The determination of independent risk factors for MP-BSI relied on logistic regression analysis. Additionally, the crude outcomes were compared. ResultsA total of 435 patients with MP were recruited, with 18.9% (82/435) having MP-BSI. The median age was 62 (interquartile range, 51,72) years, and 74.5% of the patients were male. Multivariate analysis revealed that immunosuppression, community-acquired MP (CA-MP), time from initial to targeted antibiotic use, high Sequential Organ Failure Assessment (SOFA) score, increased respiratory rate, and elevated γ-GT level (all p < 0.05) were independent risk factors for MP-BSI, while targeted treatment with linezolid was a protective factor. Patients with MP-BSI had a longer duration of hospitalization (median days, 27.5 vs. 19, p = 0.001), a higher 28-day mortality rate (24.4% vs. 11.0%, p = 0.001), and a higher in-hospital mortality rate (26.8% vs. 14.7%, p = 0.009) than those with MP alone. ConclusionSecondary MRSA-BSI among patients with MP is not rare. Immunosuppression, CA-MP, time from initial to targeted antibiotic use, high SOFA score, increased respiratory rate and elevated γ-GT level are all independent risk factors for MP-BSI; however, linezolid, as a targeted antibiotic, is a protective factor. Moreover, patients with MP may have worse clinical outcomes when they develop MRSA-BSI.

Molecular characterization and virulence gene profiling of methicillin-resistant Staphylococcus aureus associated with bloodstream infections in southern China.

Methicillin-resistant Staphylococcus aureus (MRSA) causes an enormous illness burden, including skin and soft tissue infections (SSTIs), pneumonia, bloodstream infections (BSI), and sepsis. BSI are associated with significant patient morbidity and mortality worldwide. However, limited information is available on MRSA-related BSI in China. This study aimed to investigate the molecular characterization of 77 MRSA isolates recovered from hospitalized patients with BSI between 2012 and 2020 at three first-class tertiary hospitals in southern China based on multilocus sequence typing (MLST), spa typing, and staphylococcal cassette chromosome mec (SCCmec) typing. Overall, 13 clonal complexes (CCs) were identified, with CC59 and CC5 being the largest clusters, indicating high genetic diversity among BSI-causing MRSA isolates. ST59 was the most prevalent MLST type (22.1%). ST5/ST764-MRSA SCCmec II was the predominant adult MRSA clone, whereas ST59-MRSA SCCmec IV was the most common pediatric MRSA clone. ST5-t2460, ST764-t1084, and ST59-t437 were the most common types of adult MRSA isolates, whereas ST59-t437 and ST59-t172 were the predominant types of children's MRSA isolates. ST59-SCCmec IV/V represented the most common clone among community acquired-MRSA isolates. ST5/ST764-SCCmec II was the most common type of hospital-associated MRSA isolate. The most prevalent toxin-encoding genes detected were hla, hld, icaA, and clfA (96.1-100%). Forty-three (100%, 43/43) isolates harbored more than 18 of the tested virulence genes in adults and eight virulence genes (23.5%, 8/34) in children. Virulence gene analysis revealed diversity among different clones: the positivity rates for the Panton-Valentine leukocidin (PVL) gene were 55.8 and 35.3% in adult and pediatric MRSA isolates, respectively; the genes seb-sei were present in all adult strains; seb-seg-sei-seo were present in all ST5, ST59, ST15, ST45, and ST22 adult strains; and seg-sei-sem-sen-seo were present in different clones, including ST15, ST45, and ST22 adult MRSA isolates and ST25, ST30, ST546, and ST72 children's MRSA isolates. Adult MRSA isolates had significantly higher antibiotic resistance rates and virulence gene prevalence than pediatric MRSA isolates. For 8 years, this study provided epidemiological data on the molecular characteristics and virulence genes in different groups of MRSA BSI in China. Our findings may provide critical information for a better understanding of MRSA BSI.

Epidemiology and infection control of Methicillin-resistant Staphylococcus aureus in a German tertiary neonatal intensive and intermediate care unit: A retrospective study (2013-2020).

In preterm and term infants who require intermediate or intensive care Methicillin-resistant Staphylococcus aureus (MRSA) infection can lead to significant morbidity. In this study MRSA colonization and infection were assessed in a mixed tertiary neonatal intensive and intermediate care unit in Germany over an 8-year period (2013–2020). We investigated patient-related factors, associated with nosocomial MRSA acquisition, and we discuss our infection control concept for MRSA. Of 3488 patients treated during the study period, 24 were MRSA positive patients, corresponding to 26 patient hospital stays. The incidence was 0.7 MRSA patients per 100 patients. The incidence density was 0.4 MRSA patient hospital stays per 1000 patient days. Twelve patients (50%) acquired MRSA in the hospital. One patient developed a hospital acquired MRSA bloodstream infection 9 days after birth (i.e., 0.03% of all patients on the ward during the study period). A total of 122 patients had to be screened to detect one MRSA positive patient. In a logistic regression model, the use of 3rd generation intravenous cephalosporin (cefotaxim) was associated with nosocomial MRSA acquisition compared with matched control patients who did not acquire MRSA. In sum, the burden of MRSA colonization and infection in the ward was low during the study period. A comprehensive infection control concept that included microbiologic colonization screening, prospective infection surveillance together with isolation and emphasis on basic hygiene measures is essential to handle MRSA in this specialized setting.

Unsuspected Clonal Spread of Methicillin-Resistant Staphylococcus aureus Causing Bloodstream Infections in Hospitalized Adults Detected Using Whole Genome Sequencing.

Though detection of transmission clusters of methicillin-resistant Staphylococcus aureus (MRSA) infections is a priority for infection control personnel in hospitals, the transmission dynamics of MRSA among hospitalized patients with bloodstream infections (BSIs) has not been thoroughly studied. Whole genome sequencing (WGS) of MRSA isolates for surveillance is valuable for detecting outbreaks in hospitals, but the bioinformatic approaches used are diverse and difficult to compare. We combined short-read WGS with genotypic, phenotypic, and epidemiological characteristics of 106 MRSA BSI isolates collected for routine microbiological diagnosis from inpatients in 2 hospitals over 12 months. Clinical data and hospitalization history were abstracted from electronic medical records. We compared 3 genome sequence alignment strategies to assess similarity in cluster ascertainment. We conducted logistic regression to measure the probability of predicting prior hospital overlap between clustered patient isolates by the genetic distance of their isolates. While the 3 alignment approaches detected similar results, they showed some variation. A gene family-based alignment pipeline was most consistent across MRSA clonal complexes. We identified 9 unique clusters of closely related BSI isolates. Most BSIs were healthcare associated and community onset. Our logistic model showed that with 13 single-nucleotide polymorphisms, the likelihood that any 2 patients in a cluster had overlapped in a hospital was 50%. Multiple clusters of closely related MRSA isolates can be identified using WGS among strains cultured from BSI in 2 hospitals. Genomic clustering of these infections suggests that transmission resulted from a mix of community spread and healthcare exposures long before BSI diagnosis.

Assessment of an online calculator's vancomycin dosing and exposure appropriateness in persons who inject drugs with methicillin-resistant Staphylococcus aureus bloodstream infections.

While the gold standard for calculating AUC involves two steady-state concentrations, online calculators can empirically estimate AUC and other pharmacokinetic (PK) parameters. In patients with potentially altered PK, such as persons who inject drugs (PWID), the reliability of these predictions is unclear. Our objectives were to characterize the PK of vancomycin in PWID with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) and to assess the impact of these PK parameters on dosing regimens when compared to regimens generated by an online calculator. This descriptive pilot study included a retrospective chart review of 48 inpatient PWID with MRSA BSI from 30 April 2018 through 31 August 2020. Demographic and clinical data along with vancomycin dosing and serum concentrations were collected. Patient-specific PK parameters were used to calculate the AUC of each empiric regimen compared with the originally predicted AUC. The study population had a median volume of distribution of 0.74L/kg, clearance of 0.081L/kg/h, elimination rate constant of 0.110/h and half-life of 6.3h. The online calculator empirically predicted 6 subtherapeutic and 42 appropriate AUC values with its recommended empiric dosing regimens. Using the actual patient-specific PK parameters, the empiric vancomycin regimens actually resulted in 21 (43.75%) underexposures, 24 (50%) appropriate exposures and 3 (6.25%) overexposures. In PWID, empiric vancomycin dosing strategies suggested by an online calculator frequently resulted in lower-than-predicted vancomycin exposures. These findings suggest that PWID with MRSA BSI may require higher and/or more frequent vancomycin doses than those empirically recommended by the population-based methods of an online calculator.

Multicenter Cohort Study of Ceftaroline Versus Daptomycin for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection.

BackgroundObservational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin.MethodsMulticenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied.ResultsTwo hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, –5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P = .034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P = .001).ConclusionsNo difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required.

Predicting Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infection Incidence Rates using Canadian Nosocomial Infection Surveillance Program (CNISP)

Methicillin-Resistant Staphylococcus aureus (MRSA) is among the most prevalent nosocomial pathogens globally, causing significant morbidity, mortality, and healthcare costs. MRSA bloodstream infection (BSI) incidence rates in Canadian hospitals have significantly risen by almost 60% and have a mortality of over 20% upon Intensive Care Unit admission. MRSA is believed to be spread through healthcare workers; thus, high hand hygiene compliancy in addition to environmental cleaning are the cornerstone countermeasures to disrupting its transmission. The Public Health Agency of Canada (PHAC), in collaboration with the Canadian Nosocomial Infection Surveillance Program (CNISP), conducts national, sentinel surveillance on healthcare-associated infections like MRSA. As a Student Epidemiologist, I developed a research proposal detailing two study objectives: 1) develop a regression model to predict all incident MRSA BSI rates among acute-care hospitals in Canada using CNISP MRSA BSI incident cases from 2000 to 2019, and 2) create a compartmental (Susceptible-Infected-Recovered-Deceased) model to determine the impact of various Infection Prevention and Control (IPC) measures on the risk of healthcare-associated MRSA BSI transmission specifically. This study hopes to demonstrate that proper IPC compliance is associated with lower incident MRSA BSI rates with the goal being to produce a manuscript draft by 2021. MRSA poses a serious threat to patient safety globally and is becoming a growing national public health concern in Canada; determining which IPC strategy is most effective at disrupting MRSA transmission is essential to reducing incidence and mortality rates.

Pneumonia, urinary tract infection, bacteremia, and Clostridioides difficile infection following major head and neck free and pedicled flap surgeries

ObjectivesMedical postoperative infections (MPIs) are important causes of morbidity following major head and neck free and pedicled flap reconstruction, but the incidence, time of onset, and microbiology are not well characterized. Materials and methodsMedical records were reviewed of all head and neck flap surgeries performed 2009–2014 at an academic medical center. Postoperative pneumonia, urinary tract infection (UTI), bloodstream infection (BSI), Clostridioides difficile (CDI), and surgical site infections (SSI) were noted. Catheter-associated UTI (CAUTI), central line-associated BSI (CLABSI), and methicillin-resistant Staphylococcus aureus (MRSA) BSI were also evaluated. ResultsFollowing 715 free (540) or pedicled (175) flap surgeries, 14.1% of patients developed ≥one MPI including pneumonia (10.6%), UTI (2.1%), BSI (0.7%), and CDI (2.4%). Onset was ≤7 days in 77%. The MPI incidence in free vs pedicled flaps was similar. By multivariate analysis, age ≥65 and clindamycin perioperative prophylaxis were associated with increased MPI risk, clean class surgery with decreased risk. The incidence of CAUTI (<1.0%), CLABSI (0.1%), and hospital-onset MRSA BSI (0.1%) was low. SSI rate (7.8% overall) was higher in patients who developed pneumonia (18.4 vs 6.6, p = 0.004). MPI cultures grew gram-negative bacilli or S. aureus in 75%. The length of stay was longer in patients who developed a MPI than those who did not (17.4 vs 10.4 days, p < 0.0001). ConclusionsOne-seventh of major head and neck flap surgeries were complicated by MPIs, three-quarters of infections developed within 1 week postoperatively. Gram-negative bacilli and S. aureus were the predominant pathogens.

Daptomycin versus Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection with or without Endocarditis: A Systematic Review and Meta-Analysis.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of invasive infections, mainly bloodstream infections (BSI) with or without endocarditis. The purpose of this meta-analysis was to compare vancomycin, the mainstay treatment, with daptomycin as therapeutic options in this context. Materials: PubMed, Embase and the Cochrane Database were searched from their inception to 15 February 2020. The primary outcome was all-cause mortality. Secondary outcomes included clinical failure, infection recurrence, persistence of infection, length-of-stay, antibiotic discontinuation due to adverse events (AEs) and 30-day re-admission. This study was registered with PROSPERO, CRD42020169413. Results: Eight studies (1226 patients, 554 vs. 672 in daptomycin vs. vancomycin, respectively) were included. No significant difference in terms of overall mortality was observed [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.40–1.33, I2 = 67%]. Daptomycin was associated with a significantly reduced risk of clinical failure (OR 0.58, 95% CI 0.38–0.89, I2 = 60%), as confirmed by pooling adjusted effect sizes (adjusted OR against the use of vancomycin 1.94, 95%CI 1.33–1.82, I2 = 41%), and was linked with fewer treatment-limiting AEs (OR 0.15, 95%CI 0.06–0.36, I2 = 19%). No difference emerged between the two treatments as secondary outcomes. Results were not robust to unmeasured confounding (E-value lower than 95% CI 1.00 for all-cause mortality). Conclusions: Against MRSA BSI, with or without endocarditis, daptomycin seems to be associated with a lower risk of clinical failure and treatment-limiting AEs compared with vancomycin. Further studies are needed to better characterize the differences between the two drugs.

Predictors of mortality in adult patients with methicillin-resistant Staphylococcus aureus bloodstream infection: a meta-analysis and systematic review.

Cases of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection have been increasing. Patients with MRSA bloodstream infection have a poor prognosis and high mortality rate. Identification of potential risk factors associated with MRSA bloodstream infection-related mortality may help improve patient outcomes. Embase, PubMed, and the Cochrane Library databases were searched to identify articles describing predictors of mortality in patients with MRSA bloodstream infections. Two investigators independently assessed articles for inclusion and data extraction. Twenty observational studies were included in the analysis. Factors associated with higher mortality were development of severe sepsis or septic shock [odds ratio (OR): 4.56, 95% CI: 3.37-6.18], congestive heart failure (OR: 1.78, 95% CI: 1.27-2.50), liver cirrhosis (OR: 1.90, 95% CI: 1.27-2.65), malignancy (OR: 1.62, 95% CI: 1.33-1.98), infective endocarditis (OR: 2.05, 95% CI: 1.35-3.11), nosocomial infection (OR: 2.80, 95% CI: 1.41-5.55), intensive care unit admission (OR: 3.08, 95% CI: 1.49-6.36) and inappropriate empirical antimicrobial treatment (OR: 2.25, 95% CI: 1.16-4.36); removal of the eradicable foci was a protective factor (OR: 0.51, 95% CI: 0.40-0.63) The average APACHE II score at the time of diagnosis of MRSA bloodstream infection was considerably higher in patients who did not survive than in those who survived [weighted mean difference (WMD): 5.81, 95% CI: 3.03-8.59]. Patient condition, appropriate timing of antimicrobial treatment, surgical intervention and disease severity according to the APACHE II score are the most important risk factors for death in patients with MRSA bloodstream infections.

Neddylation Alleviates Methicillin-Resistant Staphylococcus aureus Infection by Inducing Macrophage Reactive Oxygen Species Production.

Neddylation, a posttranslational modification in which NEDD8 is covalently attached to target proteins, has emerged as an endogenous regulator of innate immunity. However, the role of neddylation in methicillin-resistant Staphylococcus aureus (MRSA) infection remains unknown. In this study, we found that neddylation was activated after MRSA infection in vivo and in vitro. Inhibition of neddylation with MLN4924 promoted injury of liver and kidneys in C57BL/6 mice with MRSA bloodstream infection and increased mortality. Blockade of neddylation, either pharmacologically (MLN4924, DI591) or through the use of Uba3 small interfering RNA, inhibited Cullin3 neddylation and promoted Nrf2 accumulation, thus reducing reactive oxygen species (ROS) induction and bacterial killing ability in mouse peritoneal macrophages. In summary, our findings suggest that activation of neddylation in macrophages plays a critical protective role against MRSA infection by increasing ROS production, partially by signaling through the NEDD8-Cullin3-Nrf2-ROS axis. Furthermore, our results may provide a new non-antibiotic treatment strategy for MRSA infection through targeting of neddylation.

Methicillin-Resistant Staphylococcus Aureus Bacteremia: Epidemiology, Clinical Characteristics, Risk Factors, and Outcomes in a Tertiary Care Center in Riyadh, Saudi Arabia.

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) has become increasingly common in hospitals worldwide. In an era of pandemics, it is important to understand all types of infectious diseases in order to control its outcome and reduce mortality rates related to it. This study aims to identify the epidemiology of MRSA bloodstream infection, risk factors, and mortality in King Abdulaziz Medical City in Riyadh.MethodsThis is a retrospective chart review study from January 2013 to June 2017. All patients with positive blood culture for MRSA at King Abdulaziz Medical City (KAMC), which is a tertiary care center in Riyadh, Saudi Arabia, were included. Data were extracted from electronic and paper medical records for patients who had a positive blood culture for MRSA. Data collected included demographics, microbiological details, risk factors, and 30-day mortality.ResultsFrom 2013 through June 2017, 633 Staphylococcus aureus bacteremia were reported in KAMC, of which 184 (29.1%) were MRSA with a mean age of 60±19 years. Almost all of our isolates were susceptible to vancomycin, linezolid, and tigecycline. The most common infectious syndrome these patients presented with was an endovascular infection which accounts for 30.4% while 19.9% presented as a case of pneumonia. The mortality within 30 days of collection of the positive blood culture was 20.65%. Male gender (OR = 2.33; 95% CI = 1.34-4.05; P-value = 0.003) and patients with history of recent hospital (OR = 2.34; 95% CI = 1.27-4.34; P-value = 0.007) or ICU (OR = 1.66; 95% CI = 1.09-2.52; P-value = 0.018) admissions were more likely to acquire MRSA.ConclusionsThe incidence of MRSA bacteremia at King Abdulaziz Medical City is high and increasing in conjunction with incidence rate posing a significantly high rate of mortality. Recent history of hospital admission, ICU admission and males were found to be significantly associated with higher rates of MRSA infection. Some modifiable risk factors that could be used to facilitate the reduction of MRSA acquisition rates is to avoid unnecessary hospital and ICU admissions.

Vancomycin or Daptomycin Plus a β-Lactam Versus Vancomycin or Daptomycin Alone for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections: A Systematic Review and Meta-Analysis.

Aims: Several in vitro and in vivo studies demonstrated that adding a β-lactam to vancomycin (VAN) or daptomycin (DAP) can provide synergy against methicillin-resistant Staphylococcus aureus (MRSA). However, the results from clinical studies were controversial. The objective of this systematic review and meta-analysis was to compare the efficacy and safety of using VAN or DAP plus a β-lactam (combination therapy) and using VAN or DAP alone (monotherapy) in MRSA bloodstream infections. Methods: We included randomized controlled trials and observational studies evaluating whether combination therapy can improve clinical and microbiological outcomes and safety compared to monotherapy with VAN or DAP in MRSA-related bacteremia. Results: Literature search identified 3 randomized clinical trials and 10 observational studies involving at least 1,796 patients. There were no significant associations between the combination therapy and risk of mortality within 30 days (risk ratios [RRs], 1.10, 95% confidence interval [CI], 0.82-1.46), in-hospital mortality (RR, 0.59, 95% CI, 0.31-1.13) and mortality within 60-90 days (RR, 0.91, 95% CI, 0.64-1.29). There was also no evidence that there was a difference in length of hospital stay between the combination therapy and monotherapy (mean difference, -0.41 days, 95% CI, -3.41 to 2.59). However, compared with monotherapy, combination therapy seemed to have a shorter duration of bacteremia(mean difference, -1.06 days, 95% CI, -1.53 to -0.60), a lower risk of persistent bacteremia (RR, 0.63, 95% CI, 0.51-0.79) and a lower risk of bacteremia recurrence within 60-90 days (RR, 0.61, 95% CI, 0.40-0.92). There were no statistically significant differences in the total number of adverse events, including acute kidney injury (AKI) (RR, 1.52, 95% CI, 0.84-2.73), thrombocytopenia (RR, 1.13, 95% CI, 0.74-1.73), and diarrhea (RR, 1.36, 95% CI, 0.70-2.65), between patients with combination therapy and monotherapy. In subgroup analysis, when the analysis was limited to the studies comparing using DAP plus ceftaroline with monotherapy, we found that the former had a lower risk of mortality within 30 days. In addition, a subgroup analysis limited to randomized clinical trials showed that the combination therapy was associated with a higher risk of AKI compared with using VAN or DAP alone. Conclusions: Although adding a β-lactam to standard therapy seemed to experience a higher clearance compared with monotherapy in patients with MRSA bacteremia, the combination therapy did not increase survival benefits. Based on the available evidence, the combination therapy was not supported as the routine management of MRSA-related bacteremia, and both its harms and benefits should be taken into account.

Combination ceftaroline and daptomycin salvage therapy for complicated methicillin-resistant Staphylococcus aureus bacteraemia compared with standard of care

Complicated methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSIs), particularly those with delayed culture clearance, are associated with high mortality. Combination therapy with daptomycin and ceftaroline (DAP+CPT) represents a novel therapeutic approach to MRSA-BSI owing to synergistic bactericidal activity. This study aimed to compare DAP+CPT with historical standard of care (SoC) for treatment of complicated MRSA-BSI. This single-centre retrospective cohort study included patients with complicated MRSA-BSI at University of Colorado Hospital. Patients receiving DAP+CPT for ≥48 h between November 2013 and March 2020 or SoC with vancomycin or DAP ± gentamicin and/or rifampicin from November 2011 to December 2013 were compared. The primary outcome was clinical failure defined as a composite of MRSA-related mortality and recurrent infection at 60 days. A total of 60 patients received DAP+CPT (n=30) or SoC (n=30). Median age was 56 years and median Pitt bacteremia score was 3. Common infectious sites were endovascular (63%) and musculoskeletal (40%). DAP+CPT was associated with a numerically lower incidence of clinical failure compared with SoC (20% vs. 43%; P=0.052). Multivariable analysis controlling for immunocompromised status (OR, 6.90, 95% CI 1.08-44.15), Charlson comorbidity index (OR, 1.12, 95% CI 0.90-1.39) and source control (OR, 0.35, 95% CI 0.08-1.46) associated DAP+CPT with 77% lower odds of clinical failure (OR, 0.23, 95% CI 0.06-0.89). In patients with complicated MRSA-BSI with delayed clearance, DAP+CPT trended towards lower rates of clinical failure than SoC and was significantly associated with decreased clinical failure after adjustment for baseline differences.